Inhibition of Tumor-specific Cytotoxic T-Lymphocyte Responses by Transforming Growth Factor β1

摘要: Abstract Transforming growth factor β (TGF-β) is a potent immunosuppressive cytokine that produced by neoplastic and normal cells. It has not been demonstrated directly, however, TGF-β can inhibit antigen-specific T-cell responses to tumor cells in vitro . We show here generation of antitumor cytotoxic T-lymphocyte (CTL) activity mixed-lymphocyte cultures splenocytes from DBA/2 mice immunized with the syngeneic P815 mastocytoma + Corynebacterium parvum was consistently profoundly inhibited when 0.675 10 ng/ml were added on Day 0 culture. 1 or later had little no effect. In contrast results immune mice, established tumor-bearing hosts showed variable degrees inhibition TGF-β, depending stage ongoing vivo response. Addition recombinant murine necrosis α (1,000 10,000 units/ml) partially reversed CTL while interleukin 2 nearly completely suppression. These data indicate one level at which may act production. To determine whether also any direct effect CTL, P815-specific clones derived host utilized. found proliferation rested response 5 2-dependent reactivation cytolytic affected TGF-β. previously activated inhibited. demonstrate profound inhibitory effects effector tumor-specific splenocytes, this be an indirect result suppressed production as well antiproliferative CTL.